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Abstract Introduction: Statins have pleiotropic effects, including reducing intimal hyperplasia (IH). Using unique nanoparticle (NPs), we hypothesized chitosan-functionalized polymeric NPs loaded with simvastatin (SL-cNPs) would: 1) readily associate with endothelial cells (ECs) and vascular smooth muscle cells (VSMCs); 2) affect EC and VSMC function; and 3) reduce IH compared to systemic simvastatin. Methods Human aortic ECs and VSMCs were cultured with SL-cNPs tagged with fluorescent tracer. Association of SL-cNPs was assessed by immunostaining and flow cytometry. The effect of SL-cNPs, empty cNPs (E-cNPs) and free simvastatin on cells was determined using RT-qPCR for RhoA and RhoB. Carotid artery balloon injured rats were treated intraoperatively with intraluminal saline, E-cNPs, low or high dose SL-cNPs; or with pre- and post-operative oral simvastatin plus intraoperative intraluminal saline or low dose SL-cNPs. Rats were euthanized (day 14) and IH was quantified. Results SL-cNPs readily associated with ECs and VSMCs. Low and high dose SL-cNPs induced significant increases in EC and VSMC RhoA gene expression. High dose SL-cNPs induced a significant increase in EC RhoB expression, while free simvastatin, low and high dose SL-cNPs significantly increased RhoB expression in VSMCs. In vivo, oral simvastatin plus intraluminal SL-cNPs significantly reduced IH compared to controls. Conclusion cNPs can be used as a novel vehicle to locally deliver statins to vascular cells. Although only the combination of oral simvastatin and SL-cNPs effectively reduced IH, different routes of delivery and/or concentration of SL-cNPs may allow for a more robust effect on IH prevention.
Peters et al. (Tue,) studied this question.